Pharmakogenetik der oralen Antikoagulation mit Cumarinen

The recent identification of VKORC1 has made important contributions to our understanding of the vitamin K cycle. The VKORC1 enzyme was shown to be the molecular target of coumarin drugs. Mutations and polymorphisms in coding and noncoding regions of the VKORC1 gene have been shown to cause both a partial to total coumarin resistance and coumarin sensitivity. Availability of molecular diagnostics (VKORC1, CYP2C9) and drug monitoring by HCPLC (determination of coumarin, vitamin K, and vitamin K epoxide levels) is helpful for detecting hereditary and acquired factors influencing coumarin therapy. In the future, these tools may be instrumental in designing individualized oral anticoagulation therapy regimens.     

Locomotor behavior and skeletal morphology of two sympatric pitheciine monkeys,Pithecia pithecia and Chiropotes satanas

Field observations of two sympatric pitheciine species reveal that the positional repertoire of the white-faced saki, Pithecia pithecia, is dominated by leaping behaviors, whereas the bearded saki, Chiropotes satanas, is predominantly quadrupedal. Examination and comparison of the postcranial skeletal morphologies and limb proportions of these species display numerous features associated with their respective locomotor behaviors. These observations accord with associations found in other primate and mammalian groups and with predictions based on theoretical and experimental biomechanics. Preliminary observations of the skeletal morphology of Cacajao calvus demonstrate a marked similarity to that of Chiropotes. The fossil platyrrhine Cebupithecia sarmientoi displays greater similarity to Pithecia, suggesting that its positional repertoire also included significant leaping and clinging behaviors.     

Inhibition of immune opsonin-independent phagocytosis by antibody to a pulmonary macrophage cell surface antigen

Unlike other hamster phagocytes, hamster pulmonary macrophages (PM) avidly ingest albumin-coated latex particles in the absence of serum. They also possess a highly specific cell surface antigen. To evaluate the relationship between these two characteristics, PM were incubated with mouse monoclonal antibody directed against the PM antigen. After unbound antibody was removed, the amount of bound antibody and the phagocytic capability of PM were measured by flow cytometry and fluorescence microscopy. Maximum antibody binding produced a 25% inhibition of ingestion. Particle attachment was not affected. This effect was antigen specific, since neither a nonspecific mouse myeloma protein of the same subclass nor a mouse antibody that bound to another hamster surface antigen had any effect on binding or ingestion. If antigen-specific F(ab')2 fragments were introduced both before and during the period of phagocytosis, the inhibition of particle ingestion approached 100%. Particle binding increased at low F(ab')2 concentrations but declined at higher concentrations. Because calcium may play a role in the ingestion process, the effect of antibody on 45Ca uptake was evaluated. It was observed that antigen-specific F(ab')2 fragments stimulated 45Ca uptake, whereas control antibodies did not. These results suggest that the antigen reacting with our anti-hamster PM monoclonal antibody is involved in immune opsonin-independent phagocytosis and that calcium participates in this phagocytic process.     

Nearest Neighbor Classification Rule for Mixtures of Discrete and Continuous Random Variables

In this paper very simple nonparametric classification rule for mixtures of discrete and continuous random variables is described. It is based on the method of nearest neighbor proposed by Cover and Hart (1967). The bounds on the limit of the nearest neighbor rule risks are given. Both lower and upper bound depend on the Bayes risk and the loss function. Finally the method is compared with other existing methods on some practical data set.     

IgG production kinetics in serum free media

Summary A murine hybridoma (455) was cultured in four different serum free media formulations, and a newborn calf serum supplemented medium was used as a basis of comparison. The serum supplemented medium supports a higher cell growth rate and results in a higher IgG titer. However, the antibody secretion rate on a per cell basis is higher in the serum free media, indicating that serum could be inhibitory to antibody secretion. The results identify the possibility of a least eliminating serum during the monoclonal antibody production phase.